Tools that allow inducible and reversible depletion of target proteins are critical for biological studies. The plant-derived auxin-inducible degradation system (AID) enables the degradation of target proteins tagged with the AID motif. This system has been recently employed in mammalian cells as well as in C. elegans and Drosophila. To test the utility of the AID approach in the nervous system, we used circadian locomotor rhythms as a model and applied the AID method to temporally and spatially degrade PERIOD (PER), a critical pacemaker protein in Drosophila. We found that the period locus can be efficiently tagged with the AID motif by CRISPR/Cas9-based genome editing without disrupting PER function. Moreover, we demonstrated that the AID system could be used to induce rapid and efficient protein degradation in the nervous system as shown by effects on circadian and sleep behaviors. Furthermore, the protein degradation by AID was rapidly reversible after auxin removal. Together, our results show that the AID system provides a powerful tool for behavior studies in Drosophila.

The circadian clock controls daily rhythms in animal physiology, metabolism, and behavior, such as the sleep‐wake cycle. Disruption of circadian rhythms has been revealed in many diseases including neurodegenerative disorders. Interestingly, patients with many neurodegenerative diseases often show problems with circadian clocks even years before other symptoms develop. Here we review the recent studies identifying the association between circadian rhythms and several major neurodegenerative disorders. Early intervention of circadian rhythms may benefit the treatment of neurodegeneration.